Endothelin, a peptide inhibitor of Na(+)-K(+)-ATPase in intact renaltubular epithelial cells.
Endothelin, a peptide inhibitor of Na(+)-K(+)-ATPase in intact renaltubular epithelial cells.
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内皮素，完整肾小管上皮细胞中 Na( )-K( )-ATP 酶的肽抑制剂。
DOI：
10.1152/ajpcell.1989.257.6.c1101
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Brenner,BM
中科院分区：
文献类型：
--
作者：
Zeidel,ML;Brady,HR;Kone,BC;Gullans,SR;Brenner,BM
内皮素是血管内皮细胞释放的一种有效的血管收缩剂，可以在体内诱导尿钠排泄。这些研究检查了兔近端小管 (PT) 和内髓集合管 (IMCD) 细胞悬液中内皮素对 Na+ 转运的调节。内皮素使 IMCD 细胞的耗氧量 (QO2) 降低 18 +/- 1%，但不会改变 PT 细胞的 QO2。在 IMCD 细胞中，内皮素在约 5 x 10(-12) M 时最大程度地抑制 QO2。多项证据表明，内皮素通过抑制 Na(+)-K(+)-ATP 酶来降低 QO2。 1) 在哇巴因之后，内皮素不再对 QO2 产生进一步的抑制作用，并且削弱了两性霉素 B 对 QO2 的刺激作用（不存在内皮素时为 +29 +/- 4%，存在内皮素时为 0 +/- 5%；n = 6 种制剂，P 小于 0.001）。 2) 内皮素在 10 秒时抑制哇巴因敏感的 86Rb+ 摄取 46.6 +/- 8.6%，在 30 秒时抑制 35.4 +/- 5.3%，而 60 分钟时的摄取没有改变。 3)向IMCD细胞添加内皮素诱导净K+流出，初始速率为32.2 +/- 4.8 nmol.min-1.mg Protein-1，与Na(+)-K(+)-ATP酶的抑制一致。与在完整细胞中观察到的反应相反，在透化的 IMCD 细胞中，内皮素不抑制哇巴因敏感的 ATP 酶。一些观察结果表明，前列腺素 E2 (PGE2) 介导内皮素对 Na(+)-K(+)-ATP 酶活性的抑制。 1) 在 QO2、净 K+ 通量和 86Rb+ 摄取测定中，对内皮素的反应被布洛芬阻断。 2) 内皮素和 PGE2 对哇巴因敏感的 86Rb+ 摄取具有等效的非加性抑制作用。（摘要截断为 250 字）
Endothelin, a potent vasoconstrictor released by vascular endothelial cells, can induce natriuresis in vivo. These studies examined the regulation of Na+ transport by endothelin in suspensions of rabbit proximal tubule (PT) and inner medullary collecting duct (IMCD) cells. Endothelin reduced oxygen consumption (QO2) by 18 +/- 1% in IMCD cells but did not alter QO2 in PT cells. In IMCD cells, endothelin inhibited QO2 half maximally at approximately 5 x 10(-12) M. Several lines of evidence indicate that endothelin reduces QO2 by inhibiting the Na(+)-K(+)-ATPase. 1) Endothelin gave no further inhibition of QO2 after ouabain and blunted the stimulatory effect of amphotericin B on QO2 (+29 +/- 4% in absence of endothelin, 0 +/- 5% in presence of endothelin; n = 6 preparations, P less than 0.001). 2) Endothelin inhibited ouabain-sensitive 86Rb+ uptake by 46.6 +/- 8.6% at 10 s and by 35.4 +/- 5.3% at 30 s without altering uptake at 60 min. 3) Addition of endothelin to IMCD cells induced a net K+ efflux with an initial rate of 32.2 +/- 4.8 nmol.min-1.mg protein-1, consistent with inhibition of the Na(+)-K(+)-ATPase. In contrast to the response observed in intact cells, in permeabilized IMCD cells endothelin did not inhibit ouabain-sensitive ATPase. Several observations indicated that prostaglandin E2 (PGE2) mediates endothelin inhibition of Na(+)-K(+)-ATPase activity. 1) The response to endothelin was blocked by ibuprofen in assays of QO2, net K+ flux, and 86Rb+ uptake. 2) Endothelin and PGE2 gave equivalent, nonadditive inhibition of ouabain-sensitive 86Rb+ uptake.(ABSTRACT TRUNCATED AT 250 WORDS)